CN105622681A - Method for preparing alkyl-beta-D-maltoside - Google Patents
Method for preparing alkyl-beta-D-maltoside Download PDFInfo
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Abstract
The invention relates to the technical field of sugar compounds and discloses a method for preparing alkyl-beta-D-maltoside. The method is characterized by comprising the steps that 1, on the catalysis condition, maltose protected by an acyl group is subjected to position 1 selective deprotection to obtain hepta-O-acyl maltose; 2, the hepta-O-acyl maltose is subjected to a reaction with trichloroacetonitrile on the catalysis condition to obtain maltose-based trichloroacetimidate; 3, the trichloroacetimidate is subjected to a straight-chain alcohol reaction on the catalysis condition to obtain alkyl-hepta-O-acyl-beta-D-maltoside; 4, the maltoside is subjected to deprotection to obtain the alkyl-beta-D-maltoside. The method for preparing the alkyl-beta-D-maltoside has the advantages that operation is easy and convenient, no high valence silver salts are adopted, the cost is low, the catalyst is cheap and easy to obtain, the reaction condition is mild, the stereoselectivity is good, separation and purification are easy, the yield is high, and no toxic heavy metal salt compounds are adopted, so that the environment-friendly purpose is achieved.
Description
Technical field
The present invention relates to sugar compounds technical field, be specifically related to a kind of method preparing alkyl-��-D-Maltose glycosides.
Background technology
Alkyl-��-D-Maltose glycosides has the structure shown in formula (I).
Alkyl polyglucoside is the nonionic surfactant that a class is novel. It is strong that it has excellent surface activity, foaming capacity and dirt-removing power, and compatibility is good, and cooperative effect is obvious, good water solubility. Easily biological-degradable, nontoxic, nonirritant, can be widely used for washing emulsifying, solubilising moisturizing, the functional product such as biological preparation, have broad application prospects in the fields such as washing, food, cosmetics and biological medicine.
Alkyl-��-D-Maltose glycosides is as the class in nonionic surfactant alkyl polyglucoside, based on its amphiphilic attribute being formed by connecting with ��-glycosidic bond by the alkyl chain part of the controlled relative flexibility of the chain length length of hydrophilic relatively stiff glycosyl part Yu oleophylic, have wide range of applications. 2002, Pillion etc. find that pentadecyl-��-D-Maltose glycosides has the strong and weak different snuffing adduction (Journalofpharmaceuticalsciences promoting insulin with cetyl-��-D-Maltose glycosides etc., 2002,91 (6), 1456-1462). 2005, Berger etc. reports decyl-��-D-Maltose glycosides and undecyl-��-D-Maltose glycosides etc. to be had human thymus A as surfactant3The ability (BiophysicalJournal.2005,89,452-464) of receptor separating-purifying from film. 2006, Jastrzebska etc. reported myristyl-��-D-Maltose glycosides etc. and affects the form of rhodopsin of g protein coupled receptor and structure (J.Biol.Chem.2006,281 (17), 11917-11922). 2008, Zhao etc. find that butyl-��-D-Maltose glycosides etc. can construct ��-1 as zymolyte for making the glycosyl of cyclodextrin transfer in such maltoside, 4-glycosidic bond (Biosci.Biotechnol.Biochem.2008,72 (11), 3006-3010). 2013, Cardoso etc. inquired into octyl group-��-D-Maltose glycosides, nonyl-��-D-Maltose glycosides etc. and has become the hydrogen bond action (Langmuir.2013,29,15778-15786) in the process of micelle and between hydrone at autohemagglutination. 2015, Gradauer etc. found that dodecyl-��-D-Maltose glycosides makes the penetrating power of FD4 significantly improve (Mol.Pharmaceutics2015,12,2245-2253) as intestinal penetration enhancers. 2016, Ali etc. reported the detection technique (JournalofLuminescence.2016,169,35-42) of dodecyl-��-D-Maltose glycosides and the interaction of bovine serum albumin.
In view of alkyl-��-D-Maltose glycosides has important using value, its synthesis is of great interest. Usually, classical preparation method system adopts the silver oxide or Disilver carbonate, poisonous mercury salt (ChemistryandPhysicsofLipids, 2004,127,47-63 that bromo sugar is expensive with fatty alcohol reaction needed; CarbohydrateResearch, 2010,345,2438-2449) promote the ��-glycosylation reaction occurring yield not high, the method there is also in the preparation process of bromo sugar and releases corrosive hydrogen bromide and acetic acid gas, it is necessary to ventilation installation that air draft is good and have the anxiety of etching apparatus and atmosphere pollution. Such as, 2000, Boyd etc. adopt bromo sugar that n-octyl-��-D-Maltose glycosides, positive decyl-��-D-Maltose glycosides and dodecyl-��-D-Maltose glycosides (Langmuir have been synthesized under Disilver carbonate effect respectively with capryl alcohol, decanol and lauryl alcohol, 2000,16 (19), 7359-7367). 2002, Pillion etc. adopt bromo sugar that corresponding ��-D-Maltose glycosides (Journalofpharmaceuticalsciences has been synthesized under Disilver carbonate effect respectively with pentadecanol and hexadecanol, 2002,91 (6), 1456-1462). 2008, Zhao etc. make bromo sugar and alcohol react correspondingly to have synthesized normal-butyl-��-D-Maltose glycosides, n-octyl-��-D-Maltose glycosides and dodecyl-��-D-Maltose glycosides (Biosci.Biotechnol.Biochem.2008 under Disilver carbonate effect, 72 (11), 3006-3010). On the other hand, adopting butter of tin etc. is Lewis acid catalyst, full acetylated maltose is made to react with fatty alcohol and deprotection, ��-different head glucosides can be occurred to the transformation of ��-different head glucosides while carrying out along with reaction, being forced to adopt the separation of resin anion (R.A.) column chromatography and recrystallization method purification subsequently after deprotection, operation is inconvenience extremely, needs to be improved (Liq.Cryst.1989,6 (3), 349-356; CarbohydrateResearch2004,339,2415-2424). Recently, Jiang Chengzhen etc. report boron trifluoride diethyl etherate catalysis method makes eight acetyl maltose and alcohol direct reaction and deprotection subsequently can prepare dodecyl-��-D-Maltose glycosides (CN103265586A), the method in a crucial step condensation reaction owing to the remaining acetic anhydride that coexists has the concentration of one of the raw material needed for occurring the anxiety that esterification generates acetate to cause condensation reaction alcohol be decreased obviously with alcohol; Although condensation reaction speed is unhappy simultaneously, but easily produce decompose and the transformation to ��-different head glucosides of the ��-different head glucosides occurs, particularly ��-the increase of different head glucosides and the generation of catabolite very easily cause purifying complex and are difficult to obtain the ��-glucosides of single configuration, and actual effect should not be good.
Therefore, find a kind of new simple to operate, mild condition, do not use valuable silver salt, less costly, stereo selectivity good, easily separated purification, productivity are higher, the synthesis that completes alkyl-��-D-Maltose glycosides without toxic heavy metal participation, eco-friendly preparation method is significant.
Summary of the invention
The present invention is to solve the various defects existed in above-mentioned prior art, a kind of method preparing alkyl-��-D-Maltose glycosides is provided, the preparation method of alkyl-�� provided by the invention-D-Maltose glycosides have easy and simple to handle, do not use high price silver salt, cost is low, catalyst is cheap and easily-available, reaction condition is gentle, stereo selectivity purification good, easily separated, productivity is higher, do not use toxic heavy metal salt compounds, eco-friendly advantage.
To achieve these goals, the present invention provides a kind of method preparing alkyl-��-D-Maltose glycosides, and the method includes:
(1) when room temperature reaction, under the amines catalyst effects such as benzylamine, the maltose that acyl group is protected is carried out 1 regioselective deacylation base protection, obtains seven-O-acyl group maltose;
(2) the described seven-O-acyl group maltose that will obtain in step (1), with dry dichloromethane for solvent, 1, react with Tritox under the effect of the catalyst such as 8-diazabicylo 11 carbon-7-alkene (english abbreviation is DBU), obtain corresponding seven-O-acyl groups-D-Maltose base tri-chloroacetimidate;
(3) at BF3��Et2Under under the effect of the catalyst such as O, with dry dichloromethane for solvent, the seven-O-acyl groups-D-Maltose base tri-chloroacetimidate obtained is contacted with straight chain alcohol, obtain alkyl-seven-O-acyl-beta-D-Maltose glycosides in step (2);
(4) alkyl-seven-O-acyl-beta-D-Maltose glycosides obtained in step (3) is carried out deprotection, obtains alkyl-��-D-Maltose glycosides, shown in described alkyl-��-D-Maltose glycosides structure such as formula (I):
Adopt said method provided by the invention prepare the alkyl-�� shown in formula (I)-D-Maltose glycosides have easy and simple to handle, do not use high price silver salt, cost is low, catalyst is cheap and easily-available, reaction condition is gentle, stereo selectivity purification good, easily separated, productivity is higher, do not use toxic heavy metal salt compounds, eco-friendly advantage. Such as; it can be seen that maltose is by the catalytic action of anhydrous sodium acetate and acetic anhydride generation acetylization reaction in the preferred case from embodiments of the invention and preparation example; obtain eight-O-acetyl group-��-D-Maltose; the latter carries out 1 deprotection with oxolane for solvent under benzylamine catalysis, and the product obtained is obtained by reacting corresponding glycosyl tri-chloroacetimidate further under DBU catalysis with Tritox. This glycosyl tri-chloroacetimidate is at BF3��Et2Reacting with straight chain alcohol under O catalysis, obtain the alkyl-��-D-Maltose glycosides of acyl group protection, the latter's deprotection in methanol solution of sodium methylate realizes the synthesis of alkyl-��-D-Maltose glycosides. The present invention is easy and simple to handle, do not use high price silver salt, cost is low, catalyst is cheap and easily-available, reaction condition is gentle, stereo selectivity purification good, easily separated, productivity is higher, do not use toxic heavy metal salt compounds, environmental friendliness, compensate for the defect of the prior aries such as above-mentioned bromo sugar method, be a kind of good method of environmentally friendly synthesis of alkyl-��-D-Maltose glycosides. And when adopting the method for the present invention to prepare the alkyl-�� shown in formula (I)-D-Maltose glycosides, the productivity of 1 selectivity deprotection, coupling reaction and deprotection reaction is all higher.
Other features and advantages of the present invention will be described in detail in detailed description of the invention part subsequently.
Detailed description of the invention
Hereinafter the specific embodiment of the present invention is described in detail. It should be appreciated that detailed description of the invention described herein is merely to illustrate and explains the present invention, it is not limited to the present invention.
The invention provides a kind of method preparing alkyl-��-D-Maltose glycosides, the method includes:
(1) in the presence of a catalyst, the maltose that acyl group is protected is carried out 1 regioselective deacylation base protection, obtains seven-O-acyl group maltose;
(2) seven-O-acyl group maltose obtained in step (1) are contacted with Tritox in the presence of a catalyst, obtain seven-O-acyl groups-D-Maltose base tri-chloroacetimidate;
(3) in the presence of a catalyst, the seven-O-acyl groups-D-Maltose base tri-chloroacetimidate obtained in step (2) is contacted with straight chain alcohol, obtain alkyl-seven-O-acyl-beta-D-Maltose glycosides of protection;
(4) alkyl-seven-O-acyl-beta-D-Maltose glycosides obtained in step (3) is carried out deprotection, obtains alkyl-��-D-Maltose glycosides, shown in described alkyl-��-D-Maltose glycosides structure such as formula (I):
When adopting method provided by the invention to prepare the alkyl-�� shown in formula (I)-D-Maltose glycosides, have operation simplicity, do not use high price silver salt, cost is low, catalyst is cheap and easily-available, reaction condition is gentle, stereo selectivity purification good, easily separated, productivity is higher, do not use toxic heavy metal salt compounds, eco-friendly advantage.
Under preferable case, in method of the present invention, in step (1), described catalyst can include at least one in benzylamine, ammonia, methylamine, ethamine, n-propylamine, n-butylamine, n-amylamine, n-hexylamine, piperidines, cyclohexylamine, aniline. More preferably, in situation, described catalyst is benzylamine. In this step, the solvent of employing can include at least one in oxolane, methanol, ethanol, dichloromethane, acetonitrile. More preferably, in situation, the solvent of employing is oxolane.
Meanwhile, in step (1), in order to make 1 regioselective deacylation base protection reaction be effectively taking place, the maltose of described acyl group protection: the mol ratio of catalyst is 1:0.5-3, it is preferred to 1:1-2.
Under preferable case, in method of the present invention, in step (2), described catalyst can include at least one in 1,8-diazabicylo 11 carbon-7-alkene (english abbreviation is DBU), Anhydrous potassium carbonate, hydrofining, sodium hydride. More preferably, in situation, described catalyst is DBU.
Meanwhile, in step (2), the seven-O-acyl group maltose obtained in step (1): Tritox: the mol ratio of catalyst is 1:1-20:0.5-3, it is preferred to 1:5-9:0.8-1.2; The dichloromethane that solvent is molecular sieve drying adopted, temperature control is subzero 10 DEG C to 40 DEG C above freezing; It is preferably room temperature.
In method of the present invention, in step (3), it is any that described straight chain alcohol includes in n-butyl alcohol, n-amyl alcohol, hexanol, n-heptanol, n-octyl alcohol, n-nonyl alcohol, Decanol, n-dodecanol, tetradecanol, cetyl alcohol, positive octadecanol; Described catalyst can include boron trifluoride diethyl etherate, and (structural formula is BF3��Et2O), at least one in trifluoromethyl sulfonic acid trimethylsilyl ester (english abbreviation is TMSOTf), it is preferred to boron trifluoride diethyl etherate.
Simultaneously; in step (3), in order to improve the productivity of alkyl-��-D-Maltose glycosides, the mol ratio of the glycosyl tri-chloroacetimidate of described protection, straight chain alcohol and catalyst is 1:1-10:1-5; it is preferably 1:1-5:1-4, more preferably 1:1-4:1-3.
Further, in step (3), the solvent of employing is at least one in the dichloromethane of molecular sieve drying, the acetonitrile of molecular sieve drying, absolute ether, anhydrous tetrahydro furan, it is preferred to the dichloromethane of molecular sieve drying; Temperature control is subzero 10 DEG C to 40 DEG C above freezing, it is preferred to adds catalyst at 0 DEG C and then naturally rises to room temperature.
In method of the present invention, in step (4), it is preferable that carry out in the basic conditions, described alkali at least one in triethylamine, ammonia, sodium hydroxide, potassium hydroxide, Feldalat NM, Sodium ethylate, it is most preferred that for Feldalat NM. In this step, the solvent of use is methanol, and temperature control is 0-40 DEG C, it is preferred to room temperature.
In method of the present invention, each described reaction is all implemented under agitation, and the present invention is also unrestricted for the speed of stirring; Simultaneously, to each response time in the method for the invention, there is no particular limitation, those skilled in the art can select according to practical situation, adopt the degree that carbohydrate chemistry conventional method is undertaken by means detection reactions such as TLC point plates, when being found that by detection the conversion ratio of raw material reaches 99%, during even more than 99%, and when the size of product spot is not further added by, namely predicate reaction end.
When the present invention reaches reaction end for each reaction described, there is no particular limitation for the method for how stopped reaction, it is possible to adopting the conventional use of various methods of those skilled in the art, the present invention does not repeat them here.
In the present invention, in described each reaction, it is possible to mixture when adopting various conventional method that each reaction reaches terminal carries out post processing respectively. This is not had special requirement and restriction by the present invention. Under preferable case, the mixture that the present invention adopts when each reaction reaches terminal with the following method carries out post processing respectively, but the method for the present invention is not limited to this.
In the present invention, in step (1), it is possible to adopt rotary evaporation in vacuo method to remove solvent, then with methanol and ethyl acetate mixed solvent (VMethanol: VEthyl acetate=6:1) carry out settlement separate, sucking filtration, washing, dry, obtain seven-O-acetyl group-D-Maltose.
In the present invention; in step (2); rotary evaporation in vacuo method can be adopted to concentrate reactant mixture when reaching terminal in hot bath, then adopt conventional column chromatography separation method separation acquisition seven-O-acyl-beta-D-Maltose base tri-chloroacetimidate.
In the present invention, in step (3), it is possible to the mixture reaching terminal is passed through washing, concentration, column chromatography for separation, recrystallization, obtains the alkyl-��-D-Maltose glycosides of acyl group protection.
In the present invention, in step (4), it is possible to adopting acidic materials is that nertralizer neutralizes the reactant mixture reaching terminal. The preferred described nertralizer of the present invention can be at least one in acetic acid, hydrochloric acid and cation exchange resin. More preferably in situation, described nertralizer is the one in acetic acid or cation exchange resin. When employing acetic acid is nertralizer, the last handling process such as column chromatography for separation and/or recrystallization method can be adopted, obtain alkyl-��-D-Maltose glycosides. When employing cation exchange resin is nertralizer, the last handling process such as column chromatography for separation and/or recrystallization method can be adopted, obtain alkyl-��-D-Maltose glycosides.
In method of the present invention, the maltose of described acyl group protection, it is possible to adopt conventional carbohydrate chemistry method by making the maltose obtaining acyl group protection by oneself.
In method of the present invention, the method for the maltose preparing the protection of described acyl group includes: under catalytic condition, maltose reacts with protective agent. The protective agent used can be conventional use of various protective agents in this area. In order to obtain the maltose of the higher acyl group protection of productivity, and to acyl group protection maltose can carry out more abundant in subsequent reactions process, namely the productivity of the product obtained is higher, protective agent of the present invention includes at least one in acetic anhydride, propionic andydride, pivalic acid acid anhydride, benzoyl oxide, chloroacetic chloride, propionyl chloride, pivaloyl chloride, Benzenecarbonyl chloride., when adopt anhydride time corresponding catalyst for the corresponding anhydrous sodium salt of this anhydride maybe when adopt acyl chlorides time corresponding catalyst be pyridine; Preferred described protective agent is at least one in acetic anhydride and Benzenecarbonyl chloride.; Further being preferably acetic anhydride, corresponding preferred catalyst is anhydrous sodium acetate. Described maltose and protectant mol ratio are 1:10-50, it is preferred to 1:13-18; Temperature control 80-130 DEG C, it is preferred to 100-120 DEG C. There is no particular limitation for this response time for the present invention, when adopting carbohydrate chemistry conventional method by being found that by TLC point plate the size of the disappearance of raw material speckle and product spot is not further added by, namely predicates reaction end.
In the present invention; when maltose and protective agent are prepared in the course of reaction of the maltose of described acyl group protection under catalytic condition; when finding that raw material speckle had disappeared already and the size of product spot no longer increases up to reaction end by TLC point plate; can adopt and the reactant liquor obtained is poured in appropriate frozen water and stirs rapidly; a large amount of white solid now occurs, continues stirred for several hour, successively sucking filtration; wash, dry, the maltose of homemade acyl group protection can be obtained.
In the present invention, it is also possible to include the above-mentioned product obtained after drying is carried out recrystallization, to the not special restriction of the method for described recrystallization, it is preferable that the solvent used by described recrystallization can be methanol, water, ethanol etc. or corresponding mixed solvent.
In method of the present invention, described maltose is a kind of saccharide compound easily purchased, it is possible to obtains by being purchased (Shanghai Aladdin biochemical technology limited company), but be not restricted to that the product that the said firm provides.
A kind of preferred embodiment according to the present invention, in method of the present invention, the synthesis of the maltose of acetyl group protection can carry out according to following reaction equation:
A kind of preferred embodiment according to the present invention, in method of the present invention, in step (1), described reaction can carry out according to following reaction equation:
A kind of preferred embodiment according to the present invention, in method of the present invention, in step (2), described reaction can carry out according to following reaction equation:
A kind of preferred embodiment according to the present invention, in method of the present invention, in step (3), described reaction can carry out according to following reaction equation:
A kind of preferred embodiment according to the present invention, in method of the present invention, in step (4), described reaction can carry out according to following reaction equation:
Hereinafter will be described the present invention by embodiment, preparation example and comparative example. In case of no particular description, the various reagent used in following example, preparation example and comparative example are all from commercially available. And adopt nuclear magnetic resonance, NMR (BRUKER company of Switzerland, model is BRUKER-400MHz nuclear magnetic resonance analyser), polariscope (company of PE company of the U.S., model is Model341 type polariscope) and melting point apparatus (Gongyi, Henan Ying Yu Yu Hua instrument plant, model is X-4 numerical monitor micro melting point apparatus) characterize synthesized various intermediate and product in embodiment, preparation example and comparative example.
Preparation example 1
Maltose (83.4mmol) and 1501.2mmol acetic anhydride is added in 500mL tri-neck round-bottomed flask, it is dividedly in some parts 85.2mmol anhydrous sodium acetate after stirring 30min at 100 DEG C, continue heating and rise to 120 DEG C, be incubated 120 DEG C of reactions until TLC detection reacts completely. Reactant liquor poured in trash ice water and stir rapidly, a large amount of white solid now occurs, continuing stir about 12h, sucking filtration, washing, dry. Carry out recrystallization with methanol and water mixed solvent, obtain eight-O-acetyl group-D-Maltose white solid, productivity 86.2%.
Preparation example 2
Maltose (83.4mmol) and 1334.4mmol acetic anhydride is added in 500mL tri-neck round-bottomed flask, it is dividedly in some parts 85.2mmol anhydrous sodium acetate after stirring 30min at 100 DEG C, continue heating and rise to 120 DEG C, be incubated 120 DEG C of reactions until TLC detection reacts completely. Reactant liquor poured in trash ice water and stir rapidly, a large amount of white solid now occurs, continuing stir about 12h, sucking filtration, washing, dry. Carry out recrystallization with methanol and water mixed solvent, obtain eight-O-acetyl group-D-Maltose white solid, productivity 85.4%.
Preparation example 3
Maltose (83.4mmol) and 1084.2mmol acetic anhydride is added in 500mL tri-neck round-bottomed flask, it is dividedly in some parts 85.2mmol anhydrous sodium acetate after stirring 30min at 100 DEG C, continue insulation 100 DEG C reaction until TLC detection reaction no longer carries out, then reactant liquor poured in trash ice water and stir rapidly, a large amount of white solid now occurs, continues stir about 12h, sucking filtration, washing, dry. Carry out recrystallization with methanol and water mixed solvent, obtain eight-O-acetyl group-D-Maltose white solid, productivity 77.8%.
Comparative example 1
(1) preparation of bromo sugar: in the fume hood that air draft is good; the acetic anhydride of 521.3mmol is added in 250mL tri-neck round-bottomed flask; ice-water bath cools down; stirring is lower adds 1.12mmol perchloric acid; it is dividedly in some parts maltose (34.75mmol); control reaction temperature less than 40 DEG C, continue stirring until TLC detection acetylization reaction is complete. Dripping phosphorus tribromide 48.65mmol in above-mentioned reaction bulb, control reaction temperature, less than 40 DEG C, changes ice-water bath cooling into, is slowly added to 140.1mmol water, controls reaction temperature less than 20 DEG C, continues stirring until TLC detection bromo-reaction is complete. With dchloromethane, reactant liquor is poured in frozen water, stirred for several minute, filter, saturated sodium bicarbonate aqueous solution is washed till alkalescence, saturated common salt water washing, anhydrous sodium sulfate dries, and filters, concentration, vacuum drying, obtains bromo maltose slurry, and yield 83.4%, for next step reaction.
(2) synthesis of positive decyl-��-D-Maltose glycosides: add bromo maltose slurry (6.95mmol) that step (1) is obtained in 100mL round-bottomed flask, useThe dichloromethane of molecular sieve drying dissolves, and adds 10.43mmol Decanol and 6.95mmol Disilver carbonate and a small amount of iodine, reaction is stirred at room temperature until TLC detection condensation reaction is complete. Filtering, filtrate uses aqueous solution of sodium bisulfite, saturated sodium bicarbonate aqueous solution and saturated common salt solution washing successively, and anhydrous sodium sulfate dries, and filters, concentrated filtrate, adopts column chromatography for separation (VPetroleum ether: VEthyl acetate=3:1), with methanol and water mixed solvent recrystallization, obtain white solid. Adding 30mL absolute methanol in this solid, drip mass fraction Feldalat NM/methanol solution than 15%, adjustment pH value is 9-10, and stirring reaction is until TLC detection reacts completely. Being neutralized to pH with 732 type cationic resin is 7, filters, is concentrated into dry, with methanol and ethyl acetate mixed solvent recrystallization, obtains positive decyl-��-D-Maltose glycosides white solid, yield 41.7%.
Comparative example 2
The synthesis of n-hexyl-��-D-Maltose glycosides: add bromo maltose slurry (6.95mmol) that the step (1) in comparative example 1 is obtained in 100mL round-bottomed flask, useThe dichloromethane of molecular sieve drying dissolves, and adds 10.43mmol hexanol and 6.95mmol Disilver carbonate and a small amount of iodine, reaction is stirred at room temperature until TLC detection condensation reaction is complete. Filtering, filtrate uses aqueous solution of sodium bisulfite, saturated sodium bicarbonate aqueous solution and saturated common salt solution washing successively, and anhydrous sodium sulfate dries, and filters, concentrated filtrate, adopts column chromatography for separation (VPetroleum ether: VEthyl acetate=3:1), with methanol and water mixed solvent recrystallization, obtain white solid. Adding 30mL absolute methanol in this solid, drip mass fraction Feldalat NM/methanol solution than 15%, adjustment pH value is 9-10, and stirring reaction is until TLC detection reacts completely. Being neutralized to pH with 732 type cationic resin is 7, filters, is concentrated into dry, with methanol and ethyl acetate mixed solvent recrystallization, obtains n-hexyl-��-D-Maltose glycosides white solid, yield 40.2%.
Comparative example 3
The synthesis of n-hexadecyl-��-D-Maltose glycosides: add bromo maltose slurry (6.95mmol) that the step (1) in comparative example 1 is obtained in 100mL round-bottomed flask, useThe dichloromethane of molecular sieve drying dissolves, and adds 10.43mmol cetyl alcohol and 6.95mmol Disilver carbonate and a small amount of iodine, reaction is stirred at room temperature until TLC detection condensation reaction is complete. Filtering, filtrate uses aqueous solution of sodium bisulfite, saturated sodium bicarbonate aqueous solution and saturated common salt solution washing successively, and anhydrous sodium sulfate dries, and filters, concentrated filtrate, adopts column chromatography for separation (VOil Ether: VEthyl acetate=4:1), with methanol and water mixed solvent recrystallization, obtain white solid. Adding 30mL absolute methanol in this solid, drip mass fraction Feldalat NM/methanol solution than 15%, adjustment pH value is 9-10, and stirring reaction is until TLC detection reacts completely. Being neutralized to pH with 732 type cationic resin is 7, filters, is concentrated into dry, with methanol and ethyl acetate mixed solvent recrystallization, obtains n-hexadecyl-��-D-Maltose glycosides white solid, yield 41.1%.
Comparative example 4
The synthesis of positive decyl-��-D-Maltose glycosides: add bromo maltose slurry (8.34mmol) that the step (1) in comparative example 1 is obtained in 100mL round-bottomed flask, useThe dichloromethane of molecular sieve drying dissolves, and adds 25.02mmol Decanol and 8.34mmol Disilver carbonate and a small amount of iodine, reaction is stirred at room temperature until TLC detection condensation reaction is complete. Filtering, filtrate uses aqueous solution of sodium bisulfite, saturated sodium bicarbonate aqueous solution and saturated common salt solution washing successively, and anhydrous sodium sulfate dries, and filters, concentrated filtrate, adopts column chromatography for separation (VPetroleum ether: VEthyl acetate=3:1), with methanol and water mixed solvent recrystallization, obtain white solid. Adding 30mL absolute methanol in this solid, drip mass fraction Feldalat NM/methanol solution than 15%, adjustment pH value is 9-10, and stirring reaction is until TLC detection reacts completely. Adopting second acid for adjusting pH value is 7, and concentration adopts column chromatography (VEthyl acetate��VMethanol=6:1) separate, with methanol and ethyl acetate mixed solvent recrystallization, obtain positive decyl-��-D-Maltose glycosides white solid, yield 37.6%.
Embodiment 1
(1) in 500mL round-bottomed flask, eight-O-acetyl group-D-Maltose (44.76mmol) that preparation example 1 is obtained is added; dissolve with 130mL oxolane; add benzylamine (67.14mmol); stirring reaction is until TLC detection reacts completely; dropping acetic acid; regulating pH value is 7, makes reaction terminating. Concentration of reaction solution, then with methanol and ethyl acetate (VMethanol: VEthyl acetate=6:1) settle, sucking filtration, adopt methanol washing, dry, obtain seven-O-acetyl group-D-Maltose solid, productivity 86.2%, be directly used as the raw material of next step reaction.
(2) in 500mL round-bottomed flask, add seven-O-acetyl group-D-Maltose (27.18mmol) that step (1) is obtained, use The dichloromethane of molecular sieve drying dissolves, and under condition of ice bath, adds Tritox (217.44mmol), stirring, dropping DBU (27.18mmol), naturally rises to room temperature, continues stirring reaction until TLC detection reacts completely. Concentration of reaction solution, column chromatography for separation (VPetroleum ether: VEthyl acetate=2:1), obtain seven-O-acetyl group-D-Maltose base tri-chloroacetimidate, productivity 81.7%.
(3) in 100mL round-bottomed flask, add seven-O-acetyl group-D-Maltose base tri-chloroacetimidate (7.76mmol) that step (2) is obtained, useThe dichloromethane of molecular sieve drying dissolves, and adds Decanol (23.28mmol), drips BF under condition of ice bath3��Et2O (23.28mmol), is raised to room temperature naturally, continues stirring reaction until TLC detection reacts completely. Successively with saturated sodium bicarbonate aqueous solution and saturated common salt water washing, concentrate organic facies, adopt column chromatography (VPetroleum ether��VEthyl acetate=3:1) separate, with methanol and water mixed solvent recrystallization, obtain positive decyl-seven-O-acetyl group-��-D-Maltose glycosides white powder, productivity 65.3%.
(4) in 100mL round-bottomed flask, positive decyl-seven-O-acetyl group-��-D-Maltose (5.04mmol) and the 30mL absolute methanol that step (3) prepares is added; dropping mass fraction is than the Feldalat NM/methanol solution being 15%; adjustment pH value is 9-10, and stirring reaction is until TLC detection reacts completely. Adding cation exchange resin adjustment pH value is 7, and sucking filtration, filtrate concentrates, and adopts acetate-methanol mixed solvent recrystallization, obtains positive decyl-��-D-Maltose glycosides white solid, productivity 87.1%.
Embodiment 2
(1) with (1) step in embodiment 1.
(2) with (2) step in embodiment 1.
(3) in 100mL round-bottomed flask, add seven-O-acetyl group-D-Maltose base tri-chloroacetimidate (7.13mmol) that the step (2) in embodiment 1 is obtained, useThe dichloromethane of molecular sieve drying dissolves, and adds hexanol (21.39mmol), adds dropping BF under condition of ice bath3��Et2O (21.39mmol), is raised to room temperature naturally, continues stirring reaction until TLC detection reacts completely. Successively with saturated sodium bicarbonate aqueous solution and saturated common salt water washing, concentrate organic facies, adopt column chromatography (VPetroleum ether��VEthyl acetate=3:1) separate, with methanol and water mixed solvent recrystallization, obtain n-hexyl-seven-O-acetyl group-��-D-Maltose glycosides white powder, productivity 60.1%.
(4) in 100mL round-bottomed flask, n-hexyl-seven-O-acetyl group-��-D-Maltose (4.21mmol) and the 30mL absolute methanol that step (3) prepares is added; dropping mass fraction is than the Feldalat NM/methanol solution being 15%; adjustment pH value is 9-10, and stirring reaction is until TLC detection reacts completely. Adding cation exchange resin adjustment pH value is 7, and sucking filtration, filtrate concentrates, and adopts acetate-methanol mixed solvent recrystallization, obtains n-hexyl-��-D-Maltose glycosides white solid, productivity 83.9%.
Embodiment 3
(1) with (1) step in embodiment 1.
(2) with (2) step in embodiment 1.
(3) in 100mL round-bottomed flask, add seven-O-acetyl group-D-Maltose base tri-chloroacetimidate (7.05mmol) that the step (2) in embodiment 1 is obtained, useThe dichloromethane of molecular sieve drying dissolves, and adds cetyl alcohol (21.15mmol), adds dropping BF under condition of ice bath3��Et2O (21.15mmol), is raised to room temperature naturally, continues stirring reaction until TLC detection reacts completely. Successively with saturated sodium bicarbonate aqueous solution and saturated common salt water washing, concentrate organic facies, adopt column chromatography (VPetroleum ether��VEthyl acetate=4:1) separate, with methanol and water mixed solvent recrystallization, obtain n-hexadecyl-seven-O-acetyl group-��-D-Maltose glycosides white powder, productivity 63.0%.
(4) in 250mL round-bottomed flask, n-hexadecyl-seven-O-acetyl group-��-D-Maltose (4.41mmol) and the 50mL absolute methanol that step (3) prepares is added; dropping mass fraction is than the Feldalat NM/methanol solution being 15%; adjustment pH value is 9-10, and stirring reaction is until TLC detection reacts completely. Adding cation exchange resin adjustment pH value is 7, and sucking filtration, filtrate concentrates, and adopts acetate-methanol mixed solvent recrystallization, obtains n-hexadecyl-��-D-Maltose glycosides white solid, productivity 88.3%.
Embodiment 4
(1) in 500mL round-bottomed flask, eight-O-acetyl group-D-Maltose (28.91mmol) that preparation example 1 is obtained is added; dissolve with 90mL oxolane; add benzylamine (28.91mmol); stirring reaction is until TLC detection reacts completely; dropping acetic acid; regulating pH value is 7, makes reaction terminating. Concentration of reaction solution, then with methanol and ethyl acetate (VMethanol:VEthyl acetate=6:1) settle, sucking filtration, adopt methanol washing, dry, obtain seven-O-acetyl group-D-Maltose, productivity 85.9%, be directly used as the raw material of next step reaction.
(2) in 250mL round-bottomed flask, add seven-O-acetyl group-D-Maltose (15.96mmol) that step (1) is obtained, use The dichloromethane of molecular sieve drying dissolves, and under condition of ice bath, adds Tritox (143.64mmol), stirring, dropping DBU (19.15mmol), naturally rises to room temperature, continues stirring reaction until TLC detection reacts completely. Concentration of reaction solution, column chromatography for separation (VPetroleum ether: VEthyl acetate=2:1), obtain seven-O-acetyl group-D-Maltose base tri-chloroacetimidate, productivity 85.3%.
(3) in 100mL round-bottomed flask, add seven-O-acetyl group-D-Maltose base tri-chloroacetimidate (6.78mmol) that step (2) is obtained, useThe dichloromethane of molecular sieve drying dissolves, and adds Decanol (27.12mmol), drips BF under condition of ice bath3��Et2O (20.34mmol), is raised to room temperature naturally, continues stirring reaction until TLC detection reacts completely. Successively with saturated sodium bicarbonate aqueous solution and saturated common salt water washing, concentrate organic facies, adopt column chromatography (VPetroleum ether��VEthyl acetate=3:1) separate, obtain positive decyl-seven-O-acetyl group-��-D-Maltose glycosides white powder, productivity 69.2%.
(4) in 100mL round-bottomed flask, positive decyl-seven-O-acetyl group-��-D-Maltose (4.66mmol) and the 40mL absolute methanol that step (3) prepares is added; dropping mass fraction is than the Feldalat NM/methanol solution being 15%; adjustment pH value is 9-10, and stirring reaction is until TLC detection reacts completely. Adopting second acid for adjusting pH value is 7, and concentration adopts column chromatography (VEthyl acetate��VMethanol=6:1) separate, adopt acetate-methanol mixed solvent recrystallization, obtain positive decyl-��-D-Maltose glycosides white solid, productivity 80.1%.
Embodiment 5
(1) with (1) step in embodiment 4.
(2) with (2) step in embodiment 4.
(3) in 100mL round-bottomed flask, add seven-O-acetyl group-D-Maltose base tri-chloroacetimidate (6.75mmol) that the step (2) in embodiment 4 is obtained, useThe dichloromethane of molecular sieve drying dissolves, and adds hexanol (20.25mmol), adds dropping BF under condition of ice bath3��Et2O (20.25mmol), is raised to room temperature naturally, continues stirring reaction until TLC detection reacts completely. Successively with saturated sodium bicarbonate aqueous solution and saturated common salt water washing, concentrate organic facies, adopt column chromatography (VPetroleum ether��VEthyl acetate=3:1) separate, with methanol and water mixed solvent recrystallization, obtain n-hexyl-seven-O-acetyl group-��-D-Maltose glycosides white powder, productivity 60.9%.
(4) in 100mL round-bottomed flask, n-hexyl-seven-O-acetyl group-��-D-Maltose (4.08mmol) and the 35mL absolute methanol that step (3) prepares is added; dropping mass fraction is than the Feldalat NM/methanol solution being 15%; adjustment pH value is 9-10, and stirring reaction is until TLC detection reacts completely. Adopting second acid for adjusting pH value is 7, and concentration adopts column chromatography (VEthyl acetate��VMethanol=5:1) separate, obtain n-hexyl-��-D-Maltose glycosides white solid, productivity 80.7%.
Embodiment 6
(1) with (1) step in embodiment 4.
(2) in 100mL round-bottomed flask, add seven-O-acetyl group-D-Maltose (8.60mmol) that step (1) is obtained, use The dichloromethane of molecular sieve drying dissolves, and under condition of ice bath, adds Tritox (60.20mmol), stirring, dropping DBU (6.88mmol), naturally rises to room temperature, continues stirring reaction until TLC detection reacts completely. Concentration of reaction solution, column chromatography for separation (VPetroleum ether: VEthyl acetate=2:1), obtain seven-O-acetyl group-D-Maltose base tri-chloroacetimidate, productivity 77.6%.
(3) in 100mL round-bottomed flask, add seven-O-acetyl group-D-Maltose base tri-chloroacetimidate (6.64mmol) that step (2) is obtained, useThe dichloromethane of molecular sieve drying dissolves, and adds cetyl alcohol (19.92mmol), adds dropping BF under condition of ice bath3��Et2O (19.92mmol), is raised to room temperature naturally, continues stirring reaction until TLC detection reacts completely. Successively with saturated sodium bicarbonate aqueous solution and saturated common salt water washing, concentrate organic facies, adopt column chromatography (VPetroleum ether��VEthyl acetate=4:1) separate, with methanol and water mixed solvent recrystallization, obtain n-hexadecyl-seven-O-acetyl group-��-D-Maltose glycosides white powder, productivity 63.1%.
(4) in 250mL round-bottomed flask, n-hexadecyl-seven-O-acetyl group-��-D-Maltose (4.16mmol) and the 60mL absolute methanol that step (3) prepares is added; dropping mass fraction is than the Feldalat NM/methanol solution being 15%; adjustment pH value is 9-10, and stirring reaction is until TLC detection reacts completely. Adopting second acid for adjusting pH value is 7, and concentration adopts column chromatography (VEthyl acetate��VMethanol=10:1) separate, obtain n-hexadecyl-��-D-Maltose glycosides white solid, productivity 83.1%.
Embodiment 7
(1) in 250mL round-bottomed flask, eight-O-acetyl group-D-Maltose (17.62mmol) that preparation example 1 is obtained is added; dissolve with 60mL oxolane; add benzylamine (35.24mmol); stirring reaction is until TLC detection reacts completely; dropping acetic acid; regulating pH value is 7, makes reaction terminating. Concentration of reaction solution, then with methanol and ethyl acetate (VMethanol: VEthyl acetate=6:1) settle, sucking filtration, adopt methanol washing, dry, obtain seven-O-acetyl group-D-Maltose solid, productivity 81.5%, be directly used as the raw material of next step reaction.
(2) in 250mL round-bottomed flask, add seven-O-acetyl group-D-Maltose (14.21mmol) that step (1) is obtained, use The dichloromethane of molecular sieve drying dissolves, and under condition of ice bath, adds Tritox (71.05mmol), stirring, dropping DBU (11.37mmol), naturally rises to room temperature, continues stirring reaction until TLC detection reacts completely. Concentration of reaction solution, column chromatography for separation (VPetroleum ether: VEthyl acetate=2:1), obtain seven-O-acetyl group-D-Maltose base tri-chloroacetimidate, productivity 65.7%.
(3) in 100mL round-bottomed flask, add seven-O-acetyl group-D-Maltose base tri-chloroacetimidate (9.32mmol) that step (2) is obtained, useThe dichloromethane of molecular sieve drying dissolves, and adds Decanol (9.32mmol), drips BF under condition of ice bath3��Et2O (9.32mmol), is raised to room temperature naturally, continues stirring reaction until TLC detection reacts completely. Successively with saturated sodium bicarbonate aqueous solution and saturated common salt water washing, concentrate organic facies, adopt column chromatography (VPetroleum ether��VEthyl acetate=3:1) separate, with methanol and water mixed solvent recrystallization, obtain positive decyl-seven-O-acetyl group-��-D-Maltose glycosides white powder, productivity 46.9%.
(4) add, to 100mL, positive decyl-seven-O-acetyl group-��-D-Maltose (4.35mmol) and the 30mL absolute methanol that step (3) prepares; dropping mass fraction is than the Feldalat NM/methanol solution being 15%; adjustment pH value is 9-10, and stirring reaction is until TLC detection reacts completely. Adding cation exchange resin adjustment pH value is 7, and sucking filtration, filtrate concentrates, and adopts acetate-methanol mixed solvent recrystallization, obtains positive decyl-��-D-Maltose glycosides white solid, productivity 87.3%.
Embodiment 8
(1) with (1) step in embodiment 1.
(2) in 100mL round-bottomed flask, add seven-O-acetyl group-D-Maltose (10.98mmol) that the step (1) in embodiment 1 is obtained, useThe dichloromethane of molecular sieve drying dissolves, and under condition of ice bath, adds Tritox (76.86mmol), stirring, dropping DBU (13.18mmol), naturally rises to room temperature, continues stirring reaction until TLC detection reacts completely. Concentration of reaction solution, column chromatography for separation (VPetroleum ether: VEthyl acetate=2:1), obtain seven-O-acetyl group-D-Maltose base tri-chloroacetimidate, productivity 79.1%.
(3) in 100mL round-bottomed flask, add seven-O-acetyl group-D-Maltose base tri-chloroacetimidate (8.62mmol) that step (2) is obtained, useThe dichloromethane of molecular sieve drying dissolves, and adds hexanol (8.62mmol), adds dropping BF under condition of ice bath3��Et2O (17.24mmol), is raised to room temperature naturally, continues stirring reaction until TLC detection reacts completely. Successively with saturated sodium bicarbonate aqueous solution and saturated common salt water washing, concentrate organic facies, adopt column chromatography (VPetroleum ether��VEthyl acetate=3:1) separate, obtain n-hexyl-seven-O-acetyl group-��-D-Maltose glycosides white powder, productivity 52.3%.
(4) add, to 100mL, n-hexyl-seven-O-acetyl group-��-D-Maltose (4.48mmol) and the 40mL absolute methanol that step (3) prepares; dropping mass fraction is than the Feldalat NM/methanol solution being 15%; adjustment pH value is 9-10, and stirring reaction is until TLC detection reacts completely. Adding cation exchange resin adjustment pH value is 7, and sucking filtration, filtrate concentrates, and adopts column chromatography (VEthyl acetate��VMethanol=10:1) separate, adopt acetate-methanol mixed solvent recrystallization, obtain n-hexyl-��-D-Maltose glycosides white solid, productivity 80.1%.
Embodiment 9
(1) in 100mL round-bottomed flask, eight-O-acetyl group-D-Maltose (10.35mmol) that preparation example 1 is obtained is added; dissolve with 35mL oxolane; add benzylamine (13.46mmol); stirring reaction is until TLC detection reacts completely; dropping acetic acid; regulating pH value is 7, makes reaction terminating. Concentration of reaction solution, then with methanol and ethyl acetate (VMethanol: VEthyl acetate=6:1) settle, sucking filtration, adopt methanol washing, dry, obtain seven-O-acetyl group-D-Maltose solid, productivity 86.7%, be directly used as the raw material of next step reaction.
(2) in 100mL round-bottomed flask, add seven-O-acetyl group-D-Maltose (8.95mmol) that step (1) is obtained, use The dichloromethane of molecular sieve drying dissolves, and under condition of ice bath, adds Tritox (71.60mmol), stirring, dropping DBU (9.85mmol), naturally rises to room temperature, continues stirring reaction until TLC detection reacts completely. Concentration of reaction solution, pillar layer separation (VPetroleum ether: VEthyl acetate=2:1), obtain seven-O-acetyl group-D-Maltose base tri-chloroacetimidate, productivity 82.6%.
(3) in 100mL round-bottomed flask, add seven-O-acetyl group-D-Maltose base tri-chloroacetimidate (7.12mmol) that step (2) is obtained, useThe dichloromethane of molecular sieve drying dissolves, and adds cetyl alcohol (17.80mmol), adds dropping BF under condition of ice bath3��Et2O (17.80mmol), is raised to room temperature naturally, continues stirring reaction until TLC detection reacts completely. Successively with saturated sodium bicarbonate aqueous solution and saturated common salt water washing, concentrate organic facies, adopt column chromatography (VPetroleum ether��VEthyl acetate=4:1) separate, with methanol and water mixed solvent recrystallization, obtain n-hexadecyl-seven-O-acetyl group-��-D-Maltose glycosides white powder, productivity 60.2%.
(4) add, to 100mL, n-hexadecyl-seven-O-acetyl group-��-D-Maltose (4.26mmol) and the 30mL absolute methanol that step (3) prepares; dropping mass fraction is than the Feldalat NM/methanol solution being 15%; adjustment pH value is 9-10, and stirring reaction is until TLC detection reacts completely. Adopting second acid for adjusting pH value is 7, and concentration adopts column chromatography (VEthyl acetate��VMethanol=10:1) separate, obtain n-hexadecyl-��-D-Maltose glycosides white solid, productivity 82.7%.
Other normal-butyls, n-pentyl, n-heptyl, n-octyl, n-nonyl, positive dodecyl, the preparation method of n-tetradecane base and n-octadecane base-��-D-Maltose glycosides is with embodiment 1��embodiment 9.
From the result of example made above 1��preparation example 3 and embodiment 1��embodiment 9 it can be seen that adopt method provided by the invention prepare alkyl-��-D-Maltose glycosides have easy and simple to handle, do not use high price silver salt, cost is low, catalyst is cheap and easily-available, reaction condition is gentle, stereo selectivity purification good, easily separated, do not use toxic heavy metal salt compounds, eco-friendly advantage; Meanwhile, adopt the method for the present invention when preparing alkyl-��-D-Maltose glycosides, except in embodiment 7 and embodiment 8 step (3) coupling reaction productivity relatively low except, the productivity of other reactions is all higher.
The preferred embodiment of the present invention described in detail above; but, the present invention is not limited to the detail in above-mentioned embodiment, in the technology concept of the present invention; technical scheme can being carried out multiple simple variant, these simple variant belong to protection scope of the present invention.
It is further to note that, each concrete technical characteristic described in above-mentioned detailed description of the invention, in reconcilable situation, it is possible to be combined by any suitable mode, in order to avoid unnecessary repetition, various possible compound modes are no longer illustrated by the present invention separately.
Additionally, can also carry out combination in any between the various different embodiment of the present invention, as long as it is without prejudice to the thought of the present invention, it should be considered as content disclosed in this invention equally.
Claims (8)
1. the method preparing alkyl-��-D-Maltose glycosides, it is characterised in that the method comprises the following steps:
(1) in the presence of a catalyst, the maltose that acyl group is protected is carried out 1 regioselective deacylation base protection, obtains seven-O-acyl group maltose;
(2) seven-O-acyl group maltose obtained in step (1) are contacted with Tritox in the presence of a catalyst, obtain seven-O-acyl groups-D-Maltose base tri-chloroacetimidate;
(3) in the presence of a catalyst, the seven-O-acyl groups-D-Maltose base tri-chloroacetimidate obtained in step (2) is contacted with straight chain alcohol, obtains alkyl-seven-O-acyl-beta-D-Maltose glycosides;
(4) alkyl-seven-O-acyl-beta-D-Maltose glycosides obtained in step (3) is carried out deprotection, obtains alkyl-��-D-Maltose glycosides, described alkyl-��-D-Maltose glycosides structure as shown in the formula (I):
Formula (I).
2. method according to claim 1, it is characterised in that in step (1), described catalyst is at least one in benzylamine, ammonia, methylamine, ethamine, n-propylamine, n-butylamine, n-amylamine, n-hexylamine, piperidines, cyclohexylamine, aniline, it is preferred to benzylamine; The solvent that this selectivity deprotection reaction adopts is at least one in oxolane, methanol, ethanol, dichloromethane, acetonitrile, it is preferred to oxolane; The maltose of acyl group protection: the mol ratio of catalyst is 1:0.5-3, it is preferred to 1:1-2; This selectivity deprotection reaction temperature is subzero 10 DEG C to 50 DEG C above freezing, it is preferred to room temperature.
3. method according to claim 1, it is characterized in that the method preparing the maltose of described acyl group protection includes: maltose and protective agent react under catalyst action, described protective agent includes at least one in acetic anhydride, propionic andydride, pivalic acid acid anhydride, benzoyl oxide, chloroacetic chloride, propionyl chloride, pivaloyl chloride, Benzenecarbonyl chloride., when adopt anhydride time corresponding catalyst for the corresponding anhydrous sodium salt of this anhydride maybe when adopt acyl chlorides time corresponding catalyst be pyridine, preferred described protective agent is acetic anhydride, and corresponding preferred catalyst is anhydrous sodium acetate; Maltose and protectant mol ratio are 1:10-50, it is preferred to 1:13-18; Temperature control 80-130 DEG C, it is preferred to 100-120 DEG C.
4. method according to claim 1, it is characterised in that in step (2), described catalyst is at least one in 1,8-diazabicylo 11 carbon-7-alkene (english abbreviation is DBU), Anhydrous potassium carbonate, hydrofining, sodium hydride, it is preferred to DBU; Seven-O-acyl group the maltose obtained in step (1): Tritox: the mol ratio of catalyst is 1:1-20:0.5-2, it is preferred to 1:5-9:0.8-1.2; The dichloromethane that solvent is molecular sieve drying adopted in the reaction of this step, temperature control is subzero 10 DEG C to 40 DEG C above freezing; It is preferably room temperature.
5. the method according to claim 1, it is characterized in that in step (3), it is any that described straight chain alcohol includes in n-butyl alcohol, n-amyl alcohol, hexanol, n-heptanol, n-octyl alcohol, n-nonyl alcohol, Decanol, n-dodecanol, tetradecanol, cetyl alcohol, positive octadecanol; Described catalyst is that (structural formula is BF to boron trifluoride diethyl etherate3Et2O), at least one in trifluoromethyl sulfonic acid trimethylsilyl ester (english abbreviation is TMSOTf), it is preferred to boron trifluoride diethyl etherate; The maltose of protection: straight chain alcohol: the mol ratio of boron trifluoride diethyl etherate is 1:1-10:1-5, it is preferred to 1:1-5:1-4, more preferably 1:1-4:1-3; The solvent that the reaction of this step adopts is at least one in the dichloromethane of molecular sieve drying, the acetonitrile of molecular sieve drying, absolute ether, anhydrous tetrahydro furan, it is preferred to the dichloromethane of molecular sieve drying; Temperature control is subzero 10 DEG C to 40 DEG C above freezing, it is preferred to adds catalyst at 0 DEG C and then naturally rises to room temperature.
6. the method according to claim 5, it is characterised in that in step (3), adopts washing, concentration, column chromatography for separation, a series of last handling process of recrystallization, obtains alkyl-seven-O-acyl-beta-D-Maltose glycosides.
7. method according to claim 1, it is characterised in that in step (4), the catalyst used by described deprotection reaction is at least one in triethylamine, ammonia, sodium hydroxide, potassium hydroxide, Feldalat NM, Sodium ethylate, it is preferred to Feldalat NM; In this step, the solvent of use is methanol, and temperature control is 0-40 DEG C, it is preferred to room temperature.
8. the method according to claim 7, it is characterized in that in step (4), adopt in acetic acid and column chromatography and/or recrystallization, it is possible to adopt in cation exchange resin and column chromatography and/or recrystallization last handling process, obtain alkyl-��-D-Maltose glycosides.
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| CN106831900A (en) * | 2017-02-24 | 2017-06-13 | 湘潭大学 | A kind of glucoside compound |
| CN110835361A (en) * | 2019-10-21 | 2020-02-25 | 山东大学 | Sialic acid glycosyl donor and preparation method and application thereof |
| CN111187312A (en) * | 2020-01-13 | 2020-05-22 | 湘潭大学 | Simple preparation method of alkyl maltoside surfactant |
| CN111187311A (en) * | 2020-01-13 | 2020-05-22 | 湘潭大学 | 1, 2-trans-maltoside surfactant and preparation method thereof |
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